The present invention is generally directed to medical diagnostics, and more particularly to a method for predicting onset/risk of atrial fibrillation in a subject, and guiding an appropriate therapy.
Atrial fibrillation (AF) is by far the most common cardiac arrhythmia. The incidence is high and increasing. The incidence increases twofold with every decade after age 55 years with a prevalence of 5% in people over age 65 (References 5 and 27), and the lifetime risk for AF for people over age 40 is approximately 25%. The number of hospital admissions for AF more than doubled between 1984 and 1994 (Reference 7). Currently, 2.2 million people in the United States have a diagnosis of AF (Reference 36). While generally not lethal, AF reduces the quality of life and increases the risk for systemic embolization, hemodynamic instability, tachycardia-induced cardiomyopathy, and mortality (References 26 and 46). Overall, AF accounts for 15-20% of strokes in the United States, numbering around 75,000 annually (Reference 52).
The pathogenesis of AF is unknown, but studies have supported a role for both oxidative stress and inflammation. Studies of animal and human samples have shown increased myocardial oxidative stress associated with atrial fibrillation (References 9, 24, 47 and 57). Furthermore, anti-oxidants including statins, Vitamin C, polyunsaturated fatty acids, and fish oils reduce the incidence of AF in humans (References 2, 10, 11, 49, 55, 59 and 60).
Inflammation has a complex relationship with oxidative stress and also been associated with AF. There is evidence of inflammatory infiltrates in many cases of lone AF (Reference 29). Elevated levels of the inflammatory marker, C-reactive protein (CRP), are associated with AF in some studies (References 3, 15 and 20) and have been suggested as a predictor of the incidence of AF following cardioversion (References 20, 50, 54 and 75) or cardiac surgery (References 28 and 53). Interleukin-6 (IL-6) is elevated in AF, (Reference 17) and polymorphisms in the IL-6 gene predict the onset of AF after cardiac surgery (Reference 33). Moreover, anti-inflammatory agents seem to reduce the risk of atrial fibrillation (References 21, 22, 40, 56, 62, 68 and 76).
The relative importance of inflammation and oxidative stress in the pathogenesis of AF and which markers might be most strongly associated with the arrhythmia remain unclear. Therefore, we assessed differences in markers of oxidative stress and inflammation between patients with and without persistent of permanent AF.